Young, Andrew L.Challen, Grant A.Birmann, BrendaDruley, Todd E.2016-11-182016Young, Andrew L., Grant A. Challen, Brenda M. Birmann, and Todd E. Druley. 2016. “Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults.” Nature Communications 7 (1): 12484. doi:10.1038/ncomms12484. http://dx.doi.org/10.1038/ncomms12484.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:29407866Clonal haematopoiesis is thought to be a rare condition that increases in frequency with age and predisposes individuals to haematological malignancy. Recent studies, utilizing next-generation sequencing (NGS), observed haematopoietic clones in 10% of 70-year olds and rarely in younger individuals. However, these studies could only detect common haematopoietic clones—>0.02 variant allele fraction (VAF)—due to the error rate of NGS. To identify and characterize clonal mutations below this threshold, here we develop methods for targeted error-corrected sequencing, which enable the accurate detection of clonal mutations as rare as 0.0003 VAF. We apply these methods to study serially banked peripheral blood samples from healthy 50–60-year-old participants in the Nurses' Health Study. We observe clonal haematopoiesis, frequently harbouring mutations in DNMT3A and TET2, in 95% of individuals studied. These clonal mutations are often stable longitudinally and present in multiple haematopoietic compartments, suggesting a long-lived haematopoietic stem and progenitor cell of origin.en-USJournal Article2016-11-1810.1038/ncomms12484